Interaction of allosteric ligands with GABAA receptors containing one, two, or three different subunits

Eur J Pharmacol. 1996 Apr 22;301(1-3):207-14. doi: 10.1016/0014-2999(96)00066-0.

Abstract

The presence of allosteric binding sites on recombinant GABAA receptors formed after transfection of human embryonic kidney (HEK) 293 cells with alpha 1-, beta 3-, or gamma 2-subunits, or with various combinations of these subunits, was systematically investigated. From all possible subunit combinations, high affinity [3H]muscimol binding sites were induced in cells transfected with alpha 1 beta 3- or alpha 1 beta 3 gamma 2-subunits only. GABAA receptor associated [3H]flunitrazepam binding sites were induced in cells after transfection with alpha 1 gamma 2- or alpha 1 beta 3, gamma 2-subunits, and [35S]r-butylbicyclophosphorothionate (TBPS) binding sites were found in cells transfected with beta 3-, beta 3 gamma 2-, alpha 1 beta 3-, or alpha 1 beta 3 gamma 2-subunits. Binding of [35S]TBPS could be inhibited by pentobarbital, etazolate, (+)-etomidate, alphaxalone, propofol, chlormethiazole, and 4'-chlorodiazepam (Ro 5-4864) with a potency which differed in cells transfected with beta 3-, beta 3 gamma 2-, alpha 1 beta 3-, or alpha 1 beta 3 gamma 2-subunits. Results obtained indicate that receptors with different subunit composition actually can be formed in HEK cells and exhibit distinct pharmacological properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Site
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics
  • Cell Line
  • Convulsants / pharmacokinetics
  • Flunitrazepam / pharmacokinetics
  • GABA Agonists / pharmacokinetics
  • GABA Modulators / pharmacokinetics
  • GABA-A Receptor Antagonists
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism*
  • Membranes / drug effects
  • Membranes / metabolism
  • Muscimol / pharmacokinetics
  • Radioligand Assay
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism*

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Convulsants
  • GABA Agonists
  • GABA Modulators
  • GABA-A Receptor Antagonists
  • Receptors, GABA-A
  • Muscimol
  • Flunitrazepam
  • tert-butylbicyclophosphorothionate